Virtual reality in surgery

Abstract

Taurine is an amino acid that plays important roles in maintaining both the structural integrity and function of the retina. Thus, the effects of taurine, taurine analogues, and their combinations were studied in the ATP-dependent calcium ion uptake system at low calcium ion concentrations (10 microM) in a rat retinal membrane preparation. (+/-)-(trans)-2-Aminocyclopentanesulfonic acid (TAPS), a cyclic taurine analogue previously determined to inhibit ATP-dependent calcium ion uptake was demonstrated to be noncompetitive (Ki = 0.055 mM) with respect to taurine, that is, the values for the half-saturation concentrations calculated from varying concentrations of taurine compared with varying concentrations of taurine in the presence of a fixed concentration of TAPS (80 microM) did not change. However, the values for the maximal rates of change were significantly different. 1,2,3,4-Tetrahydroquinoline-8-sulfonic acid (THQS), a less potent inhibitor of ATP-dependent calcium ion uptake than TAPS, was also shown to be noncompetitive with taurine, with an inhibition constant (Ki) of 23.8 mM. Thus, it is presumed that both compounds (TAPS and THQS) are acting at receptor site(s) other than the taurine binding site. When TAPS and THQS were tested in a mixture that maintains a ratio (fixed ratio mixture) of 1 part TAPS and 25 parts THQS (by concentration, in mM), varied over a wide range of concentrations, and were then analyzed by median-effect plots and equation, the inhibitory effects are strongly synergistic, as shown by the combination index and the dose-reduction index. The parallel nature of the median-effect plots of TAPS and THQS indicates that the two inhibitors have a similar mode of action, that is, mutually exclusive. (+/-)-3-Aminotetrahydrothiophene-1,1-dioxide (ATS) and (+/-)-piperidine-3-sulfonic acid (PSA) are an agonist and partial agonist that demonstrated stimulatory effects on ATP-dependent calcium ion uptake. When tested in combination (1:1) with taurine, they were also determined to be mutually exclusive. It was demonstrated that ATS and taurine induced the same maximal rates of change of calcium ion uptake; however, PSA was less potent than taurine. The combination of taurine plus ATS was additive, whereas the combination of taurine plus PSA was synergistic. Structure-activity relationships of the taurine analogues and their topological relationships are discussed.